Gastric cancer is the third most common cancer worldwide. The majority of gastric cancers are sporadic but familial clustering is seen in more than 10% of cases. This manuscript is divided into two parts. The first part is dedicated to the non-syndromic hereditary gastric cancer, particularly the hereditary diffuse gastric cancer (HDGC) and other gastric polyposes including the recently described GAPPS (Gastric adenocarcinoma and proximal polyposis of the stomach). The second part concerns the syndromic gastric cancer, namely the HNPCC syndrome (Hereditary Non Polyposis Colorectal Cancer) occurring as part of a genetic predisposition syndrome to cancer. Recent advances in oncogenetics and next generation sequencing technology have enabled the identification of new entities. This enhancement in knowledge regarding inherited syndromes predisposing to gastric cancer has consequently improved the management of patients and their families. In this context, pathologists play a major role in identifying particular morphologic entities prompting genetic investigation. The aim of this manuscript is to provide an update on the current knowledge about hereditary gastric cancer.

Hereditary predispositions are responsible for more than 30% of or paraganglioma. Their identification is essential to optimize medical care and to offer an appropriate screening to relatives. To date, there are more than 15 known paraganglioma/pheochromocytoma predisposing genes. The most frequently involved are those encoding the succinate dehydrogenase (SDHx), accounting for half of cases and the VHL gene, causing the Von Hippel Lindau syndrome and representing approximately 20% of genetically determined cases. Patients with SDHB genes mutations have a higher risk of metastatic disease. An oncogenetic counseling is recommended to all patients developing one or several paragangliomas, isolated or associated with other tumors. Apart from the clinical presentation and in particular the syndromic forms characterized by specific tumor spectra, there is no validated morphological criterion allowing to suspect a hereditary form. On the other hand, pathologists have now access to several immunohistochemical tools allowing the identification of some hereditary forms, in particular those linked to the SDHx, VHL and FH genes. Thus, the loss of expression in immunohistochemistry of the SDHB or FH proteins orientates respectively, towards SDHx and FH genes, while the membrane expression of carbonic anhydrase IX (CA-IX) is a sensitive and specific tool pointing towards a VHL anomaly. Other immunohistochemical markers are under evaluation. A systematic SDHB immunohistochemical staining is recommended on all paragangliomas/pheochromocytomas in order to allow an early detection of the most common hereditary forms and to contribute to the interpretation of the genetic results in these patients seen in oncogenetics consultation.

Nowadays, diagnostic biomarker research is oriented on a genomic characterisation of prostate cancer (PCa). This study evaluated diagnostic values of TMPRSS2-Erg fusion transcripts expression (TE) and androgen receptor variant 7 (AR-V7) on urine (tU) and biopsic rince material (tLRB) samples.

To evaluate the impact of systematic radiological review by breast specialist radiologist of malignant breast lesion imaging on the therapeutic management of patients.

To propose updated French guidelines for non-muscle invasive (NMIBC) and muscle-invasive (MIBC) bladder cancers.

Trichoadenoma is a very rare follicular tumour with a remarkable histopathological appearance. In this article we present a series of 12 cases of trichoadenoma, as well as the anatomoclinical and dermatoscopic findings in a typical case. We discuss these findings in the light of an extensive literature research.

To determine the diagnostic accuracy of magnetic resonance imaging (MRI) for local preoperative staging in endometrial cancer in our center (Centre Hospitalier Universitaire de Nantes: CHU), since the French National Cancer Institute's surgery recommendations publication in 2010, especially for the prediction of myometrial and cervical stromal invasion.

Prostate cancer is a sensitive adenocarcinoma, in more than 80% of cases, to chemical castration, due to its hormone dependence. Locally advanced and/or high-risk cancer is defined based on clinical stage, initial prostate specific antigen serum concentration value or high Gleason score. Hormone therapy associated with radiation therapy is the standard of management and improves local control, reduces the risk of distant metastasis and improves specific and overall survival. Duration of hormone therapy, dose level of radiation therapy alone or associated with brachytherapy are controversial data in the literature. The therapeutic choice, multidisciplinary, depends on the age and comorbidity of the patient, the prognostic criteria of the pathology and the urinary function of the patient. Current research focuses on optimizing local and distant control of these aggressive forms and incorporates neoadjuvant or adjuvant chemotherapy and also new hormone therapies.

Perioperative chemotherapy is the standard strategy for localized gastric cancers. Nevertheless, this strategy seems to be inefficient, if not deleterious, for patients with tumors harboring microsatellite instability (MSI) and/or mismatch repair deficiency (dMMR), a tumor phenotype predictive for the efficacy of immune checkpoint inhibitors (ICKi).

It is paramount to identify patients whose cancer is associated with genetic susceptibility to the disease, since their long-term management depends on it. Anatomical and molecular pathologists play a key role in the process. Indeed, their diagnosis supports or even sometimes warrants germline genetic testing. For example, a colorectal cancer with mismatch repair protein expression loss suggests Lynch syndrome, while a rare type of renal cell carcinoma with fumarate hydrate expression loss is highly evocative of hereditary leiomyomatosis and renal cell carcinoma syndrome. Similarly, the presence of the T790M EGFR variant before treatment in a non-small-cell lung carcinoma warrants further testing as the variant is likely of germline origin. Patients with suspected genetic susceptibility to cancer are referred to the nearest clinical cancer genetics clinic. The cancer geneticist, assisted by a genetic counsellor, then collects detailed personal and familial information, sometimes feeds them into bioinformatics tools or clinico-pathological scores, decides whether germline genetic analysis is justified, determines which genes should be analysed and prescribes testing. Germline testing is carried out on a blood sample by expert laboratories using next generation sequencing on panels of cancer susceptibility genes. The cancer geneticists then return the result to the patient. When a pathogenic variant is identified, the patient's management is modified, with recommendations ranging from intensified surveillance to risk-reducing surgery. Treatment is sometimes adapted to the pathogenic variant. In addition, relatives can undergo genetic testing, should they wish to know whether they carry the familial variant. In the near future, we expect clinical cancer genetics to move towards strengthened partnerships with molecular pathologists and medical oncologists. Somatic genetic analyses are now routine, at least in metastatic cancer, and a proportion of the tumoral variants identified are actually of germline origin. As for the oncologists, the development of mainstreaming programs where they are allowed to prescribe germline testing under the supervision of a cancer genetics team is unavoidable.

Fibrogenesis is a universal and ubiquitous process associated with tissue healing. The impairment of tissue homeostasis resulting from the deregulation of numerous cellular actors, under the effect of specific cytokine and pro-oxidative environments can lead to extensive tissue fibrosis, organ dysfunction and significant morbidity and mortality. This situation is frequent in internal medicine, since fibrosis is associated with most organ insufficiencies (i.e. cardiac, renal, or hepatic chronic failures), but also with cancer, a condition with common pathophysiological mechanisms. Finally, fibrosis is a hallmark of numerous systemic autoimmune diseases such as connective tissue disorders (in particular systemic sclerosis), vasculitides, granulomatoses, histiocytoses, and IgG4-associated disease. Although the process leading to tissue fibrosis may be in part irreversible, new pharmacological approaches or cell therapies bring hope in the field of fibrotic conditions.

Sentinel node is defined as the first node to receive drainage from a primary tumor and seems to reflect the nodal status in the lymphatic drainage of the tumor. Sentinel node technique has modified the pathological examination of lymph nodes, with intraoperative evaluation of sentinel node, allowing immediate lymph node dissection in case of positive sentinel node, and histological ultrastratification to detect occult metastases. This is a literature review of different histological protocols of sentinel node according to different organs. Except for sentinel node in breast cancer and melanoma, intraoperative examination of sentinel node is helpful using frozen section, more sensitive than touch imprint cytology. Sentinel node should be embedded in paraffin block entirely after gross sectioning at two millimeters intervals parallel to the long axis of the node. Histological ultrastaging with serial sections can be helpful, but the number of sections and the interval between them is not codified. Three sections at 200-250 microns can identify the majority of micrometastases (<2mm and >200 microns). Systematic immunohistochemistry of sentinel node is not necessary for breast cancers, since isolated tumor cells do not modify the therapeutic strategy, but remains useful in other organs.